2. Academic Validation
  3. Synthesis and antitumor activity of novel steroidal imidazolium salt derivatives

Synthesis and antitumor activity of novel steroidal imidazolium salt derivatives

  • Eur J Med Chem. 2019 Apr 15:168:232-252. doi: 10.1016/j.ejmech.2019.02.025.
Guogang Deng 1,  Bei Zhou 2,  Jing Wang 1,  Zhuo Chen 1,  Liang Gong 3,  Yaxiao Gong 3,  Dongmei Wu 3,  Yan Li 4,  Hongbin Zhang 5,  Xiaodong Yang 6
Affiliations

Affiliations

  • 1 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China.
  • 2 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China; Key Laboratory for Forest Resources Conservation and Utilisation in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming, China.
  • 3 State Key Laboratory for Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming, 650204, PR China.
  • 4 State Key Laboratory for Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming, 650204, PR China. Electronic address: liyanb@mail.kib.ac.cn.
  • 5 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China. Electronic address: zhanghb@ynu.edu.cn.
  • 6 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China. Electronic address: xdyang@ynu.edu.cn.
PMID: 30822712 DOI: 10.1016/j.ejmech.2019.02.025
Abstract

Sixty-one novel steroidal imidazolium salt derivatives were synthesized and evaluated in vitro against a panel of human tumor cell lines. The results showed that diosgenin‒imidazolium salt derivatives displayed much higher cytotoxic activities than cholesterol‒imidazolium salts and dehydroepiandrosterone‒imidazolium salts. The SARs results suggested that the existence of substituted 5,6-dimethyl-benzimidazoles or benzimidazole ring and substitution of the imidazolyl-3α-position with a 2-bromobenzyl or 2-naphthylmethyl group could be critical for promoting cytotoxic activity. Diosgenin‒imidazolium salt a30 was found to be the most potent compound with IC50 values of 0.44-0.79 μM against five human tumor cell lines. Compound a24 showed inhibitory activity selectively against SMMC-7721 cell lines with IC50 value of 0.21 μM and 54-fold more sensitive to DDP. Moreover, compound a30 inhibited cell proliferation through inducing the G0/G1 cell cycle arrest and Apoptosis in SMMC-7721 cells.

Keywords

Antitumor activities; Cholesterol; Dehydroepiandrosterone; Diosgenin; Imidazolium salt; Structure–activity relationships.

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